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. 2016 Jul;233(14):2675-86.
doi: 10.1007/s00213-016-4313-y. Epub 2016 Apr 30.

Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo

Natalie M Zahr  1   2 , Edith V Sullivan  3 , Torsten Rohlfing  4 , Dirk Mayer  4   5 , Amy M Collins  4 , Richard Luong  6 , Adolf Pfefferbaum  3   4
Affiliations

Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo

Natalie M Zahr et al. Psychopharmacology (Berl). 2016 Jul.

Abstract

Rationale: Serious neurological concomitants of alcoholism include Wernicke's encephalopathy (WE), Korsakoff's syndrome (KS), and hepatic encephalopathy (HE).

Objectives: This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation.

Methods: Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment.

Results: Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls.

Conclusions: These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.

Keywords: Carbon tetrachloride; Hematology; Magnetic resonance; Pyrithiamine; Spectroscopy.

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Figures

Fig. 1
Fig. 1
Left: MR and treatment schedule including number of animals used at each time point and Right: weight changes over the course of the experiment for a) liver damage (carbon tetrachloride, CCl4) model, b) food deprivation (FD) model, c) and thiamine deficiency + ethanol (EtOH) model. Ctrl=control; PE=pyrithiamine-treated+EtOH; PS=pyrithiamine-treated+saline; TE=thiamine-treated+EtOH
Fig. 2
Fig. 2
MR images showing two time points (baseline and following treatment) in exemplary Ctrl (top) and CCL4-treated (bottom) animals. Arrows indicate lateral ventricles (top arrow) and cisterns (bottom arrow).
Fig. 3
Fig. 3
Volumes of lateral ventricles (left), cisterns (middle), and total CSF (lateral ventricles+cisterns+temporal pole CSF, right) in a) liver damage (CCl4) model, b) food deprivation (FD) model, c) and thiamine deficiency + ethanol (EtOH) model. Ctrl=control; PE=pyrithiamine-treated+EtOH; PS=pyrithiamine-treated+saline; TE=thiamine treated+EtOH, †p≤0.1, *p≤05.
Fig. 4
Fig. 4
Levels of N-acetylasparate (NAA), total creatine (tCr), choline-containing compounds (Cho), and glutamate (Glu) in a) liver damage (CCl4) model, b) food deprivation (FD) model, c) and thiamine deficiency + ethanol (EtOH) model. Ctrl=control; PE=pyrithiamine-treated+EtOH; PS=pyrithiamine-treated+saline; TE=thiamine treated+EtOH, †p≤0.1, *p≤05.
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References

    1. Bates TE, Williams SR, Kauppinen RA, Gadian DG. Observation of cerebral metabolites in an animal model of acute liver failure in vivo: a 1H and 31P nuclear magnetic resonance study. Journal of neurochemistry. 1989;53:102–10. - PubMed
    1. Bendszus M, Weijers HG, Wiesbeck G, Warmuth-Metz M, Bartsch AJ, Engels S, Boning J, Solymosi L. Sequential MR imaging and proton MR spectroscopy in patients who underwent recent detoxification for chronic alcoholism: correlation with clinical and neuropsychological data. American Journal of Neuroradiology. 2001;22:1926–1932. - PMC - PubMed
    1. Bluml S, Zuckerman E, Tan J, Ross BD. Proton-decoupled 31P magnetic resonance spectroscopy reveals osmotic and metabolic disturbances in human hepatic encephalopathy. Journal of neurochemistry. 1998;71:1564–76. - PubMed
    1. Boulanger Y, Labelle M, Khiat A. Role of phospholipase A(2) on the variations of the choline signal intensity observed by 1H magnetic resonance spectroscopy in brain diseases. Brain Res Brain Res Rev. 2000;33:380–9. - PubMed
    1. Butters N. The Wernicke-Korsakoff syndrome: a review of psychological, neuropathological and etiological factors. Curr Alcohol. 1981;8:205–32. - PubMed

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